RGD Reference Report - Substrate-mediated nanoparticle/gene delivery to MSC spheroids and their applications in peripheral nerve regeneration.

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Substrate-mediated nanoparticle/gene delivery to MSC spheroids and their applications in peripheral nerve regeneration.
Authors:	Tseng, TC Hsu, SH
Citation:	Tseng TC and Hsu SH, Biomaterials. 2014 Mar;35(9):2630-41. doi: 10.1016/j.biomaterials.2013.12.021. Epub 2014 Jan 2.
RGD ID:	10059363
Pubmed:	PMID:24388817 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.biomaterials.2013.12.021 (Journal Full-text)
Substrate-derived mesenchymal stem cell (MSC) spheroids show greater differentiation capacities than dispersed single cells in vitro. During spheroid formation, nanoparticles (NPs)/genes may be delivered into the cells. In this study, MSCs were conveniently labeled with superparamagnetic Fe3O4 NPs, or transfected with brain-derived neurotrophic factor (BDNF) gene, by the substrate-mediated NP/gene uptake. With the promising in vitro data showing the beneficial effect on neural development and neurotrophic factor expression, MSCs were combined with a polymeric nerve conduit to bridge a 10 mm transection gap of rat sciatic nerve. High-resolution (7-T) magnetic resonance imaging (MRI) was used to track the transplanted cells. Nerve regeneration was assessed by functional recovery and histology. Results revealed that Fe3O4 NP-labeled MSCs were successfully visualized by MRI in vivo. Animals receiving BDNF-transfected MSC spheroids demonstrated the shortest gap bridging time (<21 days), the largest regenerated nerve, and the thickest myelin sheath at 31 days. Compared to MSC single cells, the pristine or BDNF-transfected MSC spheroids significantly promoted the functional recovery of animals, especially for the BDNF-transfected MSC spheroids. The transplanted MSCs were incorporated in the regenerated nerve and differentiated into non-myelinating Schwann cells after 31 days. This study suggests that the substrate-mediated gene delivery and NP labeling may provide extra values for MSC spheroids to carry therapeutic/diagnostic agents in cell-based therapy.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
BDNF	Human	sciatic neuropathy	treatment	ISO	Bdnf (Rattus norvegicus)		RGD
Bdnf	Rat	sciatic neuropathy	treatment	IDA			RGD
Bdnf	Mouse	sciatic neuropathy	treatment	ISO	Bdnf (Rattus norvegicus)		RGD

Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Bdnf	Rat	regeneration		IDA			RGD

Genes (Rattus norvegicus)


Bdnf (brain-derived neurotrophic factor)

Genes (Mus musculus)


Bdnf (brain derived neurotrophic factor)

Genes (Homo sapiens)


BDNF (brain derived neurotrophic factor)

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Substrate-mediated nanoparticle/gene delivery to MSC spheroids and their applications in peripheral nerve regeneration.